Veljko Dragojlovic

Solvent-free Diels–Alder reactions of in situ generated cyclopentadiene

A solvent-free Diels–Alder reaction was carried out by heating a mixture of dicyclopentadiene and a dienophile. Cyclopentadiene, formed in situ, reacted with the dienophile in a thermodynamically controlled reaction. Besides being solvent-free, the described procedure allows for almost complete utilization of dicyclopentadiene and avoids handling of noxious and hazardous cyclopentadiene. The reaction worked well with dienophiles such as maleic anhydride and unsaturated esters. However, unsaturated acids were not suitable dienophiles, yielding Diels–Alder adducts in a low yield.

Diels-Alder reactions in the presence of a minimal amount of water

Abstract Diels-Alder reactions of neat reactive dienes and dienophiles are frequently vigorous and have a limited preparative value. It is possible to control the temperature of multi-gram scale Diels-Alder reactions by adding a minimal amount of water to neat reactants. In addition, the presence of water resulted in an increased reaction rate and formation of a higher purity product. The use of minimal amounts of other solvents, with lower heat capacities, did not give good results. Furthermore, some dienophiles, e.g. maleic anhydride, reacted poorly in a dilute water suspension or solution, but worked well in the presence of a minimal amount of water. This is an environmentally friendly, practical and efficient approach to preparation of Diels-Alder adducts on a multi-gram scale.

Phase-vanishing reactions with PTFE (Teflon) as a phase screen.

Phase-vanishing reactions are triphasic reactions, which involve a reagent, a liquid perfluoroalkane, and a substrate. In a phase-vanishing reaction with PTFE tape as the phase screen instead of a liquid perfluoroalkane, there is no limitation related to the density of a phase and the denser phase can be in the top layer. The reactions were faster compared to traditional PV reactions, and it was possible to carry out sequential and tandem reactions and reactions under a reflux.

Design of Phase‐Vanishing Reactions

Phase-vanishing reactions utilize a perfluorinated solvent as a liquid membrane to separate a substrate and a reagent. Since their introduction less than ten years ago, phase-vanishing reactions have become a valuable alternative to reactions that require a slow addition of a reagent. A variety of experimental designs allow reactions to be carried out under anhydrous conditions, under photolytic conditions, under solvent-free conditions, with a gas as a reagent, and under reflux.

Phase-vanishing halolactonization of neat substrates

Summary Phase-vanishing reactions are triphasic reactions which involve a reagent, a liquid perfluoroalkane as a phase screen and a substrate. The perfluoroalkane does not dissolve any of the reactants and is used to separate them. Halolactonization of neat substrates under phase-vanishing conditions avoids use of both solvents and basic reaction conditions. Both γ,δ-alkenoic acids as well as the corresponding methyl esters are suitable substrates for phase-vanishing halolactonizations. The reaction works well both on solid and liquid substrates and the products are obtained in good to excellent yields, particularly in the case of rigid bicyclic systems. Bromine (Br2) and iodine monochloride (ICl) are suitable electrophiles for bromolactonization and iodolactonization, respectively. Although in some cases iodine gave satisfactory yields of the corresponding iodolactone, it is generally inferior to iodine monochloride.

Solvent-free phase-vanishing reactions with PTFE (Teflon®) as a phase screen

Summary In a solvent-free phase-vanishing reaction with PTFE (polytetrafluoroethylene, Teflon®) tape as the phase screen, a thermometer adapter is utilized to insert a PTFE-sealed tube into the vapor phase above the substrate. Besides avoiding use of solvents, the experimental design is not dependent upon the densities of the reactants and the procedure generates little or no waste while providing the reaction products in high yield and in high purity.

Conformational analysis of cycloalkanes

Conformational analysis is a comparatively new area of organic chemistry that has been developed well after the theories of organic reactions, bonding in organic compounds and stereochemistry. It was only in the second half of twentieth century that its importance was fully recognized and its central role with respect to bonding, reactivity and stability of organic compounds was appreciated. Fundamental concepts of conformational analysis, a deeper discussion of the conformational analysis of small and common rings and an introduction into the conformational analysis of medium and large rings are presented at a level suitable for an introductory organic chemistry course. This discussion aims to provide a better understanding of the complex relationship among different types of strain, while also discussing the factors that determine stability of a particular conformation. Finally, the unique nature of each class of cycloalkanes is explored.

Properties of PTFE tape as a semipermeable membrane in fluorous reactions

Summary In a PTFE tape phase-vanishing reaction (PV-PTFE), a delivery tube sealed with PTFE tape is inserted into a vessel which contains the substrate. The reagent diffuses across the PTFE tape barrier into the reaction vessel. PTFE co-polymer films have been found to exhibit selective permeability towards organic compounds, which was affected by the presence of solvents. In this study, we attempted to establish general trends of permeability of PTFE tape to different compounds and to better describe the process of solvent transport in PV-PTFE bromination reactions. Though PTFE tape has been reported as impermeable to some compounds, such as dimethyl phthalate, solvent adsorption to the tape altered its permeability and allowed diffusion through channels of solvent within the PTFE tape. In this case, the solvent-filled pores of the PTFE tape are chemically more akin to the adsorbed solvent rather than to the PTFE fluorous structure. The solvent uptake effect, which was frequently observed in the course of PV-PTFE reactions, can be related to the surface tension of the solvent and the polarity of the solvent relative to the reagent. The lack of pores in bulk PTFE prevents solvents from altering its permeability and, therefore, bulk PTFE is impermeable to most solvents and reagents. However, bromine, which is soluble in liquid fluorous media, diffused through the bulk PTFE. A better understanding of the PTFE phase barrier will make it possible to further optimize the PV-PTFE reaction design.

Reaction of bromine with 4,5-dimethyl-1,4-cyclohexadiene-1,2-dicarboxylic acid: a green chemistry puzzle for organic chemistry students

Abstract Bromination of an alkene is a typical addition reaction covered in an introductory organic chemistry course and laboratory. In this undergraduate organic chemistry laboratory exercise, students studied the bromination of a 4,5-dimethyl-1,4-cyclohexadiene-1,2-dicarboxylic acid. The reaction has an unexpected outcome as bromination yields the aromatic product, 4,5-dimethylphthalic acid. Green chemistry modification involves application of a “bromide/peroxide reaction” with NaBr/H2O2 in an acidic medium as an in situ source of bromine. The experiment was carried out as a two-day exercise and the students integrated molecular modeling, interpretation of mass spectra, knowledge of stability of organic compounds, and knowledge of the reaction mechanisms of addition and elimination to explain the experimental outcome.

A Student-Made Inexpensive Multichannel Pipet

An inexpensive multichannel pipet designed to deliver small volumes of liquid simultaneously to wells in a multiwell plate can be prepared by students in a single laboratory period. The multichannel pipet is made of disposable plastic 1 mL syringes and drilled plastic plates, which are used to make plunger and barrel assemblies. Application of the multichannel pipet on a combinatorial chemistry chemiluminescent esters laboratory exercise is described.